PMID- 15225676
OWN - NLM
STAT- MEDLINE
DCOM- 20050208
LR  - 20150831
IS  - 1043-6618 (Print)
IS  - 1043-6618 (Linking)
VI  - 50
IP  - 3
DP  - 2004 Sep
TI  - Bioequivalence trials of rifampicin containing formulations: extrinsic and 
      intrinsic factors in the absorption of rifampicin.
PG  - 317-27
AB  - Rifampicin shows variable bioavailability from solid oral dosage forms and the 
      reasons for this variable absorption reported in literature varies from extrinsic 
      formulations factors to intrinsic variability in rifampicin absorption. Hence, we 
      have undertaken a systematic and comprehensive evaluation of all the factors to 
      study contribution of all the factors on rifampicin absorption. As a first step, 
      data from eight bioequivalence studies conducted at National Institute of 
      Pharmaceutical Education and Research (NIPER) bioavailability center was compared 
      across the trials to understand the effect of extrinsic/intrinsic factors on the 
      bioavailability of rifampicin, isoniazid and pyrazinamide. Out of eight fixed 
      dose combination (FDC) formulations, six formulations were bioequivalent for 
      rifampicin to separate formulations whereas one formulation was below and one was 
      above the limits of bioequivalence. It was observed that more variability in 
      rifampicin blood levels is associated with FDC formulations when compared to 
      rifampicin-only formulations and was attributed to complexity involved in the 
      manufacturing of FDCs. Further, one of the rifampicin-only capsule showed 
      unexpectedly lower plasma levels indicating role of physical characteristics of 
      rifampicin bulk material. It was also seen that rifampicin shows dose-dependent 
      pharmacokinetics even at the modest increase in dose due to saturation of efflux 
      system at absorption site and metabolizing enzymes for elimination. Other 
      components of FDC formulations such as isoniazid and pyrazinamide due to high 
      solubility and permeability have shown very less variability and were 
      bioequivalent to separate formulations even from formulations those were failed 
      for rifampicin. The comparison of data across the trials suggested that 
      rifampicin bioavailability problem is more attributable to the extrinsic factors 
      such as formulation or rifampicin bulk material rather than intrinsic variability 
      of rifampicin absorption.
FAU - Agrawal, Shrutidevi
AU  - Agrawal S
AD  - Department of Pharmaceutics, National Institute of Pharmaceutical Education and 
      Research (NIPER), Sector 67, Mohali, Punjab 160062, India.
FAU - Singh, Inderjit
AU  - Singh I
FAU - Kaur, Kanwal Jit
AU  - Kaur KJ
FAU - Bhade, Shantaram
AU  - Bhade S
FAU - Kaul, Chaman Lal
AU  - Kaul CL
FAU - Panchagnula, Ramesh
AU  - Panchagnula R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Meta-Analysis
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - VJT6J7R4TR (Rifampin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Analysis of Variance
MH  - Chemistry, Pharmaceutical
MH  - Clinical Trials as Topic/statistics & numerical data
MH  - Confidence Intervals
MH  - Humans
MH  - Intestinal Absorption/drug effects/*physiology
MH  - Middle Aged
MH  - Rifampin/*blood/*pharmacokinetics
MH  - Therapeutic Equivalency
EDAT- 2004/07/01 05:00
MHDA- 2005/02/09 09:00
CRDT- 2004/07/01 05:00
PHST- 2004/01/26 00:00 [accepted]
PHST- 2004/07/01 05:00 [pubmed]
PHST- 2005/02/09 09:00 [medline]
PHST- 2004/07/01 05:00 [entrez]
AID - S1043661804000271 [pii]
AID - 10.1016/j.phrs.2004.01.009 [doi]
PST - ppublish
SO  - Pharmacol Res. 2004 Sep;50(3):317-27. doi: 10.1016/j.phrs.2004.01.009.